A painful ambivalence

My patient didn’t have heart disease, and I had no reason to suspect he ever would. What he did have was chronic knee arthritis that couldn’t easily be fixed.

Vioxx had eased his pain, but its withdrawal from the market had scared him. He probably would have tried to avoid all anti-inflammatory drugs at that point, but on his next visit he shared the waiting room with an attractive, well-dressed drug representative whose suitcase was overflowing with Celebrex samples.

In the examination room, my patient -- perhaps influenced by reproductive biology in addition to the way the information was packaged and presented to make it seem irrefutable -- asked for Celebrex to replace the Vioxx he had been taking. Deflated by the Vioxx news but conditioned to believe that only a magic pill could treat his arthritis, he was still susceptible to the Celebrex hype.

Both Vioxx and Celebrex are members of the class of drugs known as Cox-2 inhibitors, which act against an enzyme that causes inflammation but theoretically spare another that protects the stomach lining. The drugs had been promoted as stomach-safe, and heavy advertising had helped Celebrex become the top-selling arthritis drug in the country (although its stomach-protective benefits have never been proved). More than 20 million prescriptions were written for Celebrex last year alone, according to IMS Health, a pharmaceutical information company.

The target of the ad campaigns’ supposition -- that people’s stomachs were being protected even as their joints were being soothed -- was as much the patient as it was the prescribing doctor.

Surveys by the Food and Drug Administration in 1999 and 2003 and by Kaiser Family Foundation in 2001 showed that more than 20% of adult consumers respond to drug ads by questioning their doctors. The same two studies revealed that almost 60% of consumers feel that the side effect warnings communicated by these ads are inadequate, but like many consumers, my patient wasn’t one to worry about possible problems until the concern was made public.

Then, as soon as the warnings about heart disease were extended to prolonged high-dose use of Celebrex, he joined the hordes that shunned that drug too. The supposed ability of Celebrex, Vioxx and Bextra to protect the stomach had been so overstated by drug companies and their representatives that my patient -- and likely many others who took these drugs -- felt betrayed when the risk of heart disease was discovered.

Now we could easily lose the entire class of Cox-2 inhibitors, despite the fact that overall they are fairly safe and might even protect against colon and breast cancer. In fact, the National Cancer Institute study that started the panic had been designed to look at the drug’s ability to reduce precancerous colon polyps.

But the widely publicized finding -- that Vioxx, and now Celebrex, could cause heart attacks in some patients -- wasn’t surprising. The Cox-2 inhibitors had been known to decrease prostaglandin I 2, a hormone-like chemical responsible for preventing clotting and inflammation. More clots and more inflammation predicts more heart attacks, but the effect of a lower dose over shorter intervals hasn’t been shown.

Try telling that to my patient. On a follow-up visit, I tried to explain “risk-benefit” and “relatively low personal risk” and “seeing risk in perspective.” But I could see that he was now viewing the drugs not as cure-alls but as villains. The dominant information he was receiving had changed from hype to panic.

I offered him the tried-and-true naproxen, which has been shown to protect the heart, but he seemed horrified. “Aleve?” he said astutely. “Hasn’t that just been shown to cause heart problems too?”

It was true that the National Institutes of Health had just suspended an Alzheimer’s prevention study after it was discovered that study participants taking naproxen (Aleve) for three years appeared to have a 50% increased risk of heart disease. This was still no reason that a patient couldn’t take an occasional Aleve or its prescription counterpart. I tried to explain that daily use of nonsteroidal anti-inflammatory drugs -- be they the Cox-2 inhibitors or the more common ibuprofen or naproxen -- could put stress on the heart after several months or years by causing the organ to retain fluids and by raising blood pressure. But my patient no longer seemed to be listening. He’d been convinced by the drug representative to use Celebrex to replace Vioxx, and he’d even reported on how well it had worked. But now, disappointed by the sudden news, he no longer had faith in the earlier sales pitch.

With Vioxx banned and Bextra, Celebrex and now Aleve seemingly down for the count, I instructed my office staff to beware of the Mobic representative. (Mobic is a nonsteroidal drug that has some of the properties of Celebrex but is not a full-fledged Cox-2 inhibitor.)

I expected my knee patient to be developing some immunity to drug hype after his two letdowns, so I was surprised to see him on his way out of the office talking to the familiar drug rep, who was on her way in. She was bringing me Mobic samples, as well as a stack of patient brochures and drug-company-funded studies. She was here to see if she could fill the vacuum left by the sudden demise of Celebrex.

I could only hope that my patient was no longer willing to listen.

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Marc Siegel is an associate professor of medicine at New York University School of Medicine. He can be reached at marc@doctorsiegel.com.